Regional structural abnormalities in thalamus in idiopathic cervical dystonia

Regional structural abnormalities in thalamus in idiopathic cervical dystonia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Regional structural abnormalities in thalamus in idiopathic cervical dystonia Yuhan Luo, Huiming Liu, Linchang Zhong, Ai Weng, Zhengkun Yang, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4000528/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 May, 2024 Read the published version in BMC Neurology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Although the thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD), the nature of the alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. Methods Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analyzed in patients with iCD. Results Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD ( P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. Conclusion This study highlights the neurobiological mechanisms of iCD related to thalamic changes. atrophy gray matter volume idiopathic cervical dystonia structural magnetic resonance imaging thalamic nuclei Figures Figure 1 Figure 2 Background Idiopathic cervical dystonia (iCD), the most common form of adult-onset dystonia, is characterized by sustained or intermittent neck movements caused by involuntary muscle contractions, resulting in abnormal movements and postures of the head, neck, and/or shoulders. In addition, patients with iCD may also have nonmotor symptoms such as mood disorders, pain, cognitive deficits, and sleep disorders, together with motor manifestations that influence daily living activities and reduce the quality of life for the patients [ 1 ]. However, the underlying cause and pathophysiology of iCD remain incompletely understood. Current neurophysiological and neuroimaging evidence shows a network model in which various brain regions play a role in the iCD pathogenesis, including the basal ganglia, thalamus, cerebellum, and sensorimotor cortex [ 2 , 3 ]. The thalamus is a key integrative hub in this network, receiving and distributing information among different brain regions [ 4 ]. Besides being a simple transponder, the thalamus contributes to signal processing within cortical hierarchies, involving in regulating emotions, arousal, cognition, wakefulness, motor control, and sensory information processing [ 5 , 6 ]. Lesion studies have shown that thalamic lesions are prone to induce CD [ 7 , 8 ], further emphasizing the potential key role of the thalamus in the iCD. Previous functional neuroimaging studies have shown increased cortical activation [ 9 ], increased regional spontaneous brain activity [ 10 ], glucose hyper-metabolism [ 11 ], and altered functional connectivity profiles [ 10 ] in the thalamus and abnormal cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit [ 12 ] in patients with iCD. Structural neuroimaging studies also revealed brain structural abnormalities in patients with iCD, but often yield diverse results. Either an increase [ 3 , 13 ] or a decrease [ 14 , 15 ]in thalamic volume has been reported in patients with iCD compared to healthy controls (HCs). Additionally, two neuroimaging studies investigating white matter microstructural abnormalities have identified increased fractional anisotropy in the bilateral thalamus in patients with iCD [ 13 , 16 ]. In these studies, the thalamus was considered a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. The thalamus contains distinct nuclei serving different functions, which may be related to different symptoms or disorders [ 17 , 18 ]. However, to our knowledge, no studies have been conducted to explore structural alterations in the distinct thalamic nuclei and their relationship to the motor and nonmotor manifestations in patients with iCD. Recently, a statistical atlas of the thalamus was constructed using ultra-high-resolution ex vivo magnetic resonance imaging (MRI) combined with in vivo data [ 19 ] (available in FreeSurfer 7, https://surfer.nmr.mgh.harvard.edu/fswiki/rel7downloads ). This tool enables the accurate measurement of each individual thalamic nuclei volume, exhibiting robust agreement with histological findings and showing excellent test-retest reliability [ 19 ]. The tool has recently been successfully employed to examine region-specific thalamic alterations in neurological disorders, including Parkinson’s disease [ 20 ], restless legs syndrome [ 21 ], and epilepsy [ 18 ], etc. Therefore, it is an ideal atlas to investigate whether and how thalamic nuclear volume change occurs in iCD. In this study, we analyzed structural MRI data from 37 patients with iCD and 37 HCs to examine: (1) whether gray matter-related abnormalities are only restricted to specific thalamic subregions; (2) whether and how alterations in volumes of thalamic subregions are associated with motor or nonmotor symptoms of patients with iCD. We hypothesized that there is heterogeneity in the morphological changes occurring within distinct thalamic nuclei in patients with iCD. Methods Participants Patients were recruited from our outpatient clinic for movement disorders between April 2019 and July 2023. The diagnosis of iCD was made by two senior neurologists based on the standard criteria [ 1 , 22 ]. Patients were excluded if they: (i) had dystonia involving other body sites in addition to neck muscles; (ii) reported evidence of stroke, Parkinson’s disease, Alzheimer’s disease, epilepsy, and traumatic brain injury; (iii) had a family history of movement disorders as well as a history of exposure to antipsychotic drugs before the onset of dystonia; (iv) had any conditions that contradicted with cerebral MRI; (v) received botulinum toxin (BoNT) injections within 3 months and oral medications for approximately 24 h before MRI scans. HCs were also recruited using the same exclusion criteria. Clinical measurements The demographics and clinical characteristics, including subjects’ age, gender, education level, handedness, duration of disease, duration of BoNT injections, and times of BoNT injections, were collected via in-person interviews before MRI scanning. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) [ 23 ], consisting of three subscales assessing motor severity, disability, and pain, was employed to evaluate symptom severity in patients with iCD by a trained neurologist. Furthermore, the Hamilton anxiety rating scale (HAMA) [ 24 ], Hamilton depression rating scale (HAMD) [ 25 ], and Mini-Mental State Examination (MMSE) were also conducted before MRI scanning to evaluate patients’ mood and cognitive function. Image acquisition Three-dimensional T1-weighted data were collected using a 3T MRI scanner (Tim Trio; Siemens, Erlangen, Germany) with a magnetization-prepared rapid-acquisition gradient-echo pulse sequence. The main parameters were repetition time = 2530 ms; echo time = 4.45 ms; inversion time = 1100 ms; flip angle = 7 ○ ; matrix dimensions = 256 mm × 256 mm; voxel size = 1 × 1 × 1 mm 3 ; and 192 slices. Image preprocessing All T1 images were processed using the standard segmentation pipeline in FreeSurfer v7.1.1 with default settings ( https://surfer.nmr.mgh.harvard.edu ). The main steps included skull stripping, Talairach registration and initialization of cortical surface reconstruction, cortical atlas registration, and subcortical parcellation. We implemented automatic parcellation of 25 thalamic nuclei in each hemisphere based on manual delineation combining in vivo and ex vivo data to quantify thalamic nuclei volumes [ 19 ]. These nuclei included anteroventral, laterodorsal and lateral posterior, ventral anterior, ventral anterior magnocellular, ventral lateral anterior, ventral lateral posterior (VLp), ventral posterolateral (VPL), and ventromedial (VM), central medial (CeM), central lateral, paracentral (Pc), centromedian (CM), and parafascicular (Pf), paratenial (Pt), Reuniens (medial ventral) (MV(Re)), mediodorsal medial magnocellular, and mediodorsal lateral parvocellular, lateral geniculate (LGN), medial geniculate (MGN), suprageniculate, pulvinar anterior, pulvinar medial, pulvinar lateral, and pulvinar inferior (Fig. 1 ). Visualized inspection confirmed that the automatic segmentation and labeling were performed accurately. Finally, Freeview ( https://surfer.nmr.mgh.harvard.edu/fswiki/FreeviewGuide/FreeviewIntroduction ) was used to show the thalamic nuclei. Calculation of thalamic nuclei volumes Between-group differences of gray matter volume in the thalamic nuclei were performed using a general linear model with age, gender, and estimated total intracranial volume as covariates. Finally, the results were corrected by a false discovery rate (FDR) with P < 0.05. Correlation analyses Correlations between abnormal thalamic nuclei volumes and TWSTRS severity scores, disability scores, pain scores, disease durations, as well as HAMA and HAMD scores in patients with iCD were performed using partial correlations with age, gender, and estimated total intracranial volume as covariates. Meanwhile, correlations between HAMA/HAMD scores and TWSTRS severity scores, disability scores, pain scores, and disease durations in patients with iCD were also analyzed using partial correlations with age and gender as covariates. Statistical significance was set as P < 0.05. Statistical analyses Age, estimated total intracranial volume, HAMA scores, HAMD scores, and MMSE scores were compared using two sample t -tests or Mann-Whitney U tests after normality testing using the Shapiro-Wilk test. Pearson χ 2 test was performed for gender comparison. All analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 25.0 (SPSS Inc., Chicago, IL). Results Demographic information and clinical characteristics Finally, 37 patients with iCD and 37 HCs were included in this study. However, the TWSTRS, HAMD, and MMSE scores were completed by 29, 36, and 35 patients with iCD, respectively. The primary reason for incomplete clinical evaluations in certain patients is their discomfort experienced from abnormal movements and postures, leading to their refusal to cooperate with long-term scale assessment. The clinical and demographic information of the 37 patients with iCD and 37 HCs are presented in Table 1 . The iCD and HCs groups did not differ in gender, estimated total intracranial volume, and MMSE scores. There were significant differences in age, HAMA, and HAMD scores between patients with iCD and HCs. Table 1 Participants’ demographics and clinical characteristics. iCD (n = 37) HCs (n = 37) P Gender (Female/Male) 17/20 24/13 0.102 Median age, years (range) 39 (19–66) 47 (33–55) 0.002 eTIV, cm 3 (range) 1459 (935–1787) 1332 (924–1883) 0.182 Median MMSE scores (range) 28 (25–30) a 29 (25–30) 0.221 Median HAMA scores (range) 6 (0–23) 1 (0–8) < 0.001 Median HAMD scores (range) 5 (0–18) b 1 (0–7) < 0.001 Disease duration, years (range) 1.5 (0.12-13) - - BoNT injections (yes/no) 14/23 - - Median TWSTRS severity scores (range) 18 (7–25) c - -- Median TWSTRS disability scores (range) 10 (0–23) c - - Median TWSTRS pain scores (range) 5.5 (0–14) c - - Note: a only 35 subjects were available. b only 36 subjects were available. c only 29 subjects were available. Abbreviations: BoNT, Botulinum toxin; eTIV, estimated total intracranial volume; iCD, idiopathic cervical dystonia; HAMA, Hamilton anxiety rating scale; HAMD, Hamilton depression rating scale; HCs, healthy controls; MMSE, Mini-Mental State Examination; and TWSTRS, Toronto Western Spasmodic Torticollis Rating Scale. Differences of the thalamic nuclei volumes Patients with iCD compared to HCs showed significant volume atrophy mainly in the CeM, CM, LGN, MGN, MV(Re), Pc, Pf, Pt, and VM nuclei ( P < 0.05, FDR corrected; Fig. 2 and Table 2 ). Trends for volume reduction of VLp ( P = 0.053, FDR corrected) and VPL ( P = 0.057, FDR corrected) nuclei were also observed in patients with iCD relative to HCs (Table 2 ). Table 2 Differences of thalamic nuclei volumes between idiopathic cervical dystonia and healthy controls. Thalamic Nucleus Abbreviations HCs iCD Corrected P Anteroventral AV 271.17 ± 39.60 269.45 ± 34.34 0.161 Central medial CeM 139.95 ± 20.46 134.94 ± 18.82 0.032* Central lateral CL 70.09 ± 18.39 68.66 ± 12.30 0.216 Centromedian CM 513.31 ± 68.61 499.73 ± 68.65 0.044* Lateraldorsal LD 51.03 ± 15.91 47.80 ± 12.75 0.208 Lateral geniculate LGN 589.09 ± 76.65 571.24 ± 79.58 0.032* Lateral posterior LP 240.39 ± 46.78 245.27 ± 29.81 0.566 Limitans (suprageniculate) L-Sg 49.47 ± 7.617 46.44 ± 10.79 0.208 Mediodorsal lateral parvocellular MDl 522.70 ± 46.75 518.38 ± 51.52 0.126 Mediodorsal medial magnocelluar MDm 1500.73 ± 161.42 1491.45 ± 163.96 0.092 Medial geniculate MGN 234.22 ± 27.30 221.81 ± 32.96 0.045* Reuniens (medial ventral) MV(Re) 25.54 ± 4.39 23.95 ± 4.70 0.032* Paracentral Pc 8.55 ± 1.17 8.41 ± 1.07 0.046* Parafascicular Pf 122.30 ± 19.79 116.67 ± 16.71 0.032* Paratenial Pt 14.97 ± 1.95 14.47 ± 1.88 0.044* Pulvinar anterior PuA 439.48 ± 38.65 452.30 ± 46.04 0.385 Pulvinar inferior PuI 521.98 ± 73.14 552.26 ± 83.20 0.658 Pulvinar lateral PuL 377.68 ± 46.59 398.42 ± 59.43 0.658 Pulvinar medial PuM 2268.23 ± 254.50 2359.87 ± 260.96 0.458 Ventral anterior VA 805.43 ± 89.78 817.68 ± 88.41 0.053 Ventral anterior magnocellular VAmc 63.33 ± 8.19 64.18 ± 7.74 0.053 Ventral lateral anterior VLa 1258.57 ± 146.47 1261.48 ± 138.49 0.053 Ventral lateral posterior VLp 1659.83 ± 206.78 1652.35 ± 195.23 0.053 Ventromedial VM 54.70 ± 8.80 51.63 ± 9.77 0.044* Ventral posterolateral VPL 1918.61 ± 250.33 1879.88 ± 261.50 0.057 Note: * represents significant results after false discovery rate (FDR) corrected with P < 0.05. Abbreviations: iCD, idiopathic cervical dystonia, and HCs, healthy controls. Correlational analyses No statistically significant correlations were observed between altered thalamic nuclei volumes and TWSTRS severity scores, disability scores, pain scores, disease durations, HAMA scores, and HAMD scores in patients with iCD after adjusting for age, gender and estimated total intracranial volume as covariates. Moreover, no statistically significant correlations were observed between HAMA/HAMD scores, TWSTRS scores, and disease durations in patients with iCD with age and gender as covariates. Discussion In this study, we observed a significant decrease in gray matter volume of specific thalamic nuclei, including CeM, CM, LGN, MGN, MV(Re), Pc, Pf, Pt, and VM in patients with iCD compared to HCs. However, no statistically significant correlations were found between these thalamic nuclei volumes and clinical characteristics in iCD group. These results support the hypothesis that regional thalamic atrophy is present in patients with iCD. The intralaminar thalamic nuclei are the primary source of excitatory input from the thalamus to the striatum [ 26 ]. The caudal group of intralaminar thalamic nuclei, namely the CM and Pf nuclei, exhibit extensive and specific connections with the basal ganglia and motor cortex, indicating potential involvement of the CM-Pf complex in motor functions. Projections from the CM and Pf are principally to the striatum, which have been shown to mediate a reciprocal thalamostriatal interaction that plays an important role in both normal and pathological movement [ 6 , 27 , 28 ]. Semenova and his colleagues discovered that movement-sensitive CM-Pf neurons exhibit selective sensitivity towards voluntary neck and hand movements in patients with iCD [ 29 ]. The most pronounced and prolonged responses were observed during movements involving neck muscles and involuntary dystonic movements, indicating the participation of the CM-Pf complex in motor behavior and its potential involvement in the pathophysiology of iCD. However, because of the absence of a control group in this study, whether these findings are directly relevant to the disease’s pathophysiology remains uncertain [ 29 ]. Our findings that CM and Pf nuclei atrophy was found in patients with iCD, may further provide evidence for their involvement in the pathophysiology of iCD. Projections from intralaminar nuclei transmit sensory signals to striatal cholinergic interneurons, eliciting a lasting pause after a burst of spikes and facilitating the integration of cortical inputs with medium spiny neurons, thereby playing a crucial role in motor function [ 30 ]. A study on mice carrying the DYT1 dystonia mutation demonstrated that an altered thalamostriatal input pattern leads to abnormal cholinergic signaling, disrupting the integration between corticostriatal and thalamostriatal, which might result in an altered motor output and predispose DYT1 gene mutation carriers to develop dystonic movements [ 31 ]. Furthermore, the thalamic rostral intralaminar nuclei, including the CeM and Pc nuclei, contribute to a range of behaviors such as sensorimotor coordination, pain modulation, cognition, and arousal processing through extensive projections to the striatum and cortex [ 6 , 32 ]. Among these nuclei, Pc contributes to motor control and processes pain signals conveyed through the spinoparabrachial pathway [ 33 – 35 ]. Sensory symptom, such as pain, is commonly reported in patients with iCD [ 1 ]; however, the underlying pathophysiological mechanism of this nonmotor manifestation remains unclear. It is reasonable to speculate that such symptom might be caused by the dysfunction of Pc nucleus in iCD. In functional MRI studies, iCD has been considered a consequence of an abnormal basal ganglia-thalamo-cortical circuit [ 12 ]. Therefore, the present findings might improve our understanding of the role of underlying structural substrates in abnormal functional brain states in iCD. The exploration of ventral thalamic nuclei is particularly interesting because of their involvement in sensorimotor information processing and being one of the major targets for surgical treatment of movement disorders [ 36 , 37 ]. It has been reported that four patients with iCD received markedly improved dystonic head tremor and dystonia after continuous bilateral thalamic ventral lateral anterior nucleus stimulation for 3 months [ 37 ]. Previous studies have identified specific patterns of neuronal activity and pathological features of the ventral thalamus in iCD [ 38 , 39 ]. Ventral thalamic neurons exhibiting dystonia-frequency activity in patients with iCD and suppression of this activity induced immediate improvement and subsequent further enhancement of dystonic movement and posture, revealing the critical role of the ventral thalamus as a key node within the network associated with dystonia [ 38 , 39 ]. In our study, we observed that patients with iCD exhibited atrophy in the thalamus’s VM, VLp, and VPL nuclei. However, the latter two nuclei differences between groups did not reach statistical significance via FDR correction. VM and VLp are known as the motor thalamus, connecting the motor areas of the cerebral cortex to the basal ganglia and cerebellum [ 40 ]. VPL, as a part of the somatosensory thalamus, receives neuronal input from the medial lemniscus and spinothalamic tracts and subsequently projects to the somatosensory cortex [ 41 ]. Furthermore, proprioceptive signals from neck muscles have historically been considered to project to the VPL nucleus [ 42 ]. Abnormalities in the integration of sensory input with control of motor output in focal dystonia have been highlighted by recent neurophysiological studies [ 43 , 44 ]. Therefore, the impaired sensory-motor integration may be partly explained by atrophy in these subregions of the thalamus in patients with iCD. Our study also revealed a higher prevalence of anxiety (37.8%) and depressive symptoms (36.1%) in patients with iCD compared to HCs. Furthermore, no significant correlations were found between HAMA/HAMD scores and the severity of motor symptoms or disease duration in patients with iCD, demonstrating that mood disorders are not simply a consequence of the movement disorder. Consistent with our results, higher rates of all psychiatric comorbidities were observed in those with iCD, with depression and anxiety being the most commonly diagnosed. Additionally, anxiety and depressive symptoms were reported to precede the onset of iCD generally and reach a peak 12 months before dystonia diagnosis, indicating that both psychiatric disorders are either prodromal symptoms or reflect shared aetiological mechanisms [ 45 – 47 ]. However, research on the mechanisms underlying anxiety or depressive symptoms in iCD is relatively limited. Current studies propose dysfunction within basal ganglia-thalamo-cortical circuits underlies motor and psychiatric manifestations in iCD [ 48 , 49 ]. In line with this hypothesis, growing evidence shows that the thalamus is one of the core dysconnectivity nodes in anxiety and depression [ 50 , 51 ]. The Re nucleus, a thalamic midline nucleus, exhibits reciprocal connections with the prefrontal cortex and hippocampus, serving as key intermediaries between these structures to regulate emotional behaviors [ 52 ]. Previous animal studies have indicated the involvement of Re nucleus dysfunction in anxiety and depressive-like behavior, which may contribute to the amalgamation of symptoms commonly observed in mental disorders such as anxiety and depression [ 53 , 54 ]. Interestingly, our study also identified atrophy in the Re nucleus in patients with iCD. Therefore, we speculate that volumetric changes in this specific thalamic region may associated with mood disorders observed in iCD. A voxel-based morphometry study investigating another type of cranial dystonia with and without depression partially supported our hypothesis by revealing volume reduction in the frontal cortex and hippocampus in the depression group. However, it is with regret that this study did not specifically examine morphometric differences within thalamic nuclei [ 55 ]. Further research is needed to understand the underlying pathophysiology of anxiety and depression in patients with iCD. Unfortunately, we did not find any correlations between atrophy in these thalamic nuclei and the severity of motor symptoms in patients with iCD, which appears to contradict the current view that implicates the involvement of the cerebello-thalamo-cortical circuit in symptom severity across different types of focal dystonia [ 56 , 57 ]. A plausible explanation could be that while a potential mechanism involves a similar network model responsible for focal dystonia, different types of dystonia originate from dysfunction in one of these regions before impacting the network more extensively. In other words, diverse forms of focal dystonia might emerge at different levels within the network, resulting in nodes with varying hierarchies of influence and specific roles. Only structural abnormalities in high-order nodes might determine the severity of symptoms in patients with iCD [ 58 ]. In line with our results, previous neuroimaging studies on patients with iCD also reported a lack of correlations between reduced thalamic volume and symptom severity [ 14 , 15 ]. Moreover, another study demonstrated that only thalamic connections to other brain regions were altered when symptoms improved after BoNT treatment in iCD, without affecting its loss of responsiveness [ 59 ]. Additionally, patients with unavailable TWSTRS scores might potentially influence the correlations between those and changes in thalamic nuclei volume. Further investigation is needed to understand the role of specific thalamic nuclei within the network model of iCD. This study has several limitations. First, our sample size is relatively small, which may limit the statistical power to detect significant differences in VLp and VPL nuclei volumes between groups after FDR corrections and correlations between atrophy in thalamic nuclei and severity in motor and nonmotor symptoms in patients with iCD. Second, the iCD and HCs groups are not matched for age, though we have regressed age and intracranial volume as covariates when comparing differences of the thalamic nuclear volumes between the two groups to mitigate its effect. Third, some patients’ lack of TWSTRS scores might influence the correlations between those and altered thalamic nuclei volume. Finally, some previous studies have demonstrated that BoNT injections can induce alterations in subcortical white matter microstructure [ 60 ] and sensorimotor network activation [ 61 ] in patients with iCD. The effects of BoNT on the thalamic nuclei volumes were not assessed in this study. Further studies should be considered to address this limitation. In conclusion, our findings demonstrate that patients with iCD exhibit atrophy in specific thalamic nuclei, particularly the intralaminar and ventral thalamic nuclei, highlighting the crucial role of the thalamus in the pathophysiology of iCD. The thalamus should not be considered a single, homogeneous structure because of potentially useful information about distinct thalamic nuclei in future dystonia studies. Abbreviations BoNT botulinum toxin CeM central medial CM centromedian FDR false discovery rate HAMA Hamilton anxiety rating scale HAMD Hamilton depression rating scale HCs healthy controls iCD idiopathic cervical dystonia LGN lateral geniculate MGN medial geniculate MMSE Mini-Mental State Examination MRI magnetic resonance imaging MV(Re) Reuniens (medial ventral) Pc paracentral Pf parafascicular Pt paratenial SPSS Statistical Package for the Social Sciences TWSTRS Toronto Western Spasmodic Torticollis Rating Scale VLp ventral lateral posterior VM ventromedial VPL ventral posterolateral Declarations Ethics statement We declare that all experiments on human subjects were conducted in accordance with the Declaration of Helsinki and that all procedures were carried out with the adequate understanding and written consent of the subjects. We also certify that formal approval to conduct the experiments described has been obtained from the human subjects review board of our institution (the Ethical Committee of the First Affiliated Hospital of Sun Yat-Sen University) and could be provided upon request. Consent for publication Not applicable. Data and materials availability statement The data and materials supporting the findings of this study are available from the corresponding author upon reasonable request. Conflicts of interest The authors report no conflict of interest. Funding This work was funded by the National Natural Science Foundation of China (grant numbers 62006220, 81771137, 82271300, and 81971103), Natural Science Foundation of Guangdong Province (grant numbers 2023A1515012739, 2016A030310132, and 2021A1515010600), Guangdong Key Project (grant numbers 2018B030335001 and 2023A1515012739), Guangzhou Key Project (grant number 202007030002), Science and Technology Program of Guangzhou (grant number 2023B03J0466), Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases (grant number 2020B1212060017), Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (grant numbers 2015B050501003 and 2020A0505020004), Shenzhen Science and Technology Research Program (grant number JCYJ20200109114816594), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment, and Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease. Author Contributions GL and JPX: Conceptualization; JPX and QMH: Methodology; YHL, HML, LCZ, AW, ZKY, YZ, JNZ, ZLO, ZCY, QXC, XXF, XDZ, WXZ, GL and JPX: Formal analysis and investigation; QXC, XXF, XDZ, QMH, KQP, and YWW: validation; YHL, HML, GL and JPX: writing-original draft; ZLO, ZCY, QMH, WXZ, YWW, GL and JPX: writing-review & editing; GL: Supervision; GL: data curation. All authors have read and approved the manuscript. Acknowledgements We would like to thank Editage (www.editage.cn) for English language editing. References Albanese A, Bhatia KP, Cardoso F, et al. Isolated Cervical Dystonia: Diagnosis and Classification. Mov Disord. 2023;38(8):1367-1378. Jinnah HA, Neychev V, Hess EJ. The Anatomical Basis for Dystonia: the Motor Network Model. Tremor Other Hyperkinet Mov (NY). 2017;7:506. Huang X, Zhang M, Li B, Shang H, Yang J. Structural and functional brain abnormalities in idiopathic cervical dystonia: a multimodal meta-analysis. Parkinsonism Relat Disord. 2022;103:153-165. 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Kumar VJ, Scheffler K, Grodd W. The structural connectivity mapping of the intralaminar thalamic nuclei. Sci Rep. 2023;13(1):11938. Semenova U, Raeva S, Sedov A. Participation of the thalamic CM-Pf complex in movement performance in patients with dystonia. Mov Disord. 2016;31(9):1398-1404. Ding JB, Guzman JN, Peterson JD, Goldberg JA, Surmeier DJ. Thalamic gating of corticostriatal signaling by cholinergic interneurons. Neuron. 2010;67(2):294-307. Sciamanna G, Tassone A, Mandolesi G, et al. Cholinergic dysfunction alters synaptic integration between thalamostriatal and corticostriatal inputs in DYT1 dystonia. J Neurosci. 2012;32(35):11991-12004. Cover KK, Mathur BN. Rostral Intralaminar Thalamus Engagement in Cognition and Behavior. Front Behav Neurosci. 2021;15:652764. Vertes RP, Linley SB, Rojas AKP. Structural and functional organization of the midline and intralaminar nuclei of the thalamus. Front Behav Neurosci. 2022;16:964644. Deng J, Zhou H, Lin JK, et al. The Parabrachial Nucleus Directly Channels Spinal Nociceptive Signals to the Intralaminar Thalamic Nuclei, but Not the Amygdala. Neuron. 2020;107(5):909-923.e6. Bourgeais L, Monconduit L, Villanueva L, Bernard JF. Parabrachial internal lateral neurons convey nociceptive messages from the deep laminas of the dorsal horn to the intralaminar thalamus. J Neurosci. 2001;21(6):2159-2165. Hamani C, Dostrovsky JO, Lozano AM. The motor thalamus in neurosurgery. Neurosurgery. 2006;58(1):146-158. Pauls KA, Hammesfahr S, Moro E, Moore AP, Binder E, El Majdoub F, Fink GR, Sturm V, Krauss JK, Maarouf M, Timmermann L. Deep brain stimulation in the ventrolateral thalamus/subthalamic area in dystonia with head tremor. Mov Disord. 2014;29:953-959. Zhuang P, Li Y, Hallett M. Neuronal activity in the basal ganglia and thalamus in patients with dystonia. Clin Neurophysiol. 2004;115(11):2542-2557. Devetiarov D, Semenova U, Usova S, et al. Neuronal activity patterns in the ventral thalamus: Comparison between Parkinson's disease and cervical dystonia. Clin Neurophysiol. 2017;128(12):2482-2490. Hintzen A, Pelzer EA, Tittgemeyer M. Thalamic interactions of cerebellum and basal ganglia. Brain Struct Funct. 2018;223(2):569-587. Behrens TE, Johansen-Berg H, Woolrich MW, Smith SM, Wheeler-Kingshott CA, Boulby PA, Barker GJ, Sillery EL, Sheehan K, Ciccarelli O, Thompson AJ, Brady JM, Matthews PM. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci. 2003;6:750-757. Uemura Y, Haque T, Sato F, Tsutsumi Y, Ohara H, Oka A, Furuta T, Bae YC, Yamashiro T, Tachibana Y, Yoshida A. Proprioceptive thalamus receiving forelimb and neck muscle spindle inputs via the external cuneate nucleus in the rat. Brain Struct Funct. 2020; 225:2177-2192. Avanzino L, Tinazzi M, Ionta S, Fiorio M. Sensory-motor integration in focal dystonia. Neuropsychologia. 2015;79:288-300. Quartarone A, Hallett M. Emerging concepts in the physiological basis of dystonia. Mov Disord. 2013;28(7):958-967. Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ. Longitudinal analysis of the relationship between motor and psychiatric symptoms in idiopathic dystonia. Eur J Neurol. 2022;29:3513-3527. Medina Escobar A, Martino D, Goodarzi Z. The prevalence of anxiety in adult-onset isolated dystonia: a systematic review and meta-analysis. Eur J Neurol. 2021;28:4238-4250. Medina Escobar A, Pringsheim T, Goodarzi Z, Martino D. The prevalence of depression in adult onset idiopathic dystonia: systematic review and metaanalysis. Neurosci Biobehav Rev.2021;125:221-230. Di Giuda D, Camardese G, Bentivoglio AR, Cocciolillo F, Guidubaldi A, Pucci L, Bruno I, Janiri L, Giordano A, Fasano A. Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging. 2012;39:1937-1948. Zoons E, Tijssen MAJ, Dreissen YEM, Speelman JD, Smit M, Booij J. The relationship between the dopaminergic system and depressive symptoms in cervical dystonia. Eur J Nucl Med Mol Imaging. 2017;44:1375-1382. Nugent AC, Davis RM, Zarate CA Jr, Drevets WC. Reduced thalamic volumes in major depressive disorder. Psychiatry Res. 2013;213(3):179-185. Zhang FF, Peng W, Sweeney JA, Jia ZY, Gong QY. Brain structure alterations in depression: psychoradiological evidence. CNS Neurosci Ther. 2018;24(11):994-1003. Cassel JC, Pereira de Vasconcelos A, Loureiro M, Cholvin T, Dalrymple-Alford JC, Vertes RP. The reuniens and rhomboid nuclei: neuroanatomy, electrophysiological characteristics and behavioral implications. Prog Neurobiol. 2013;111:34-52. Linley SB, Athanason AC, Rojas AKP, Vertes RP. Role of the reuniens and rhomboid thalamic nuclei in anxiety-like avoidance behavior in the rat. Hippocampus. 2021;31(7):756-769. Kafetzopoulos V, Kokras N, Sotiropoulos I, et al. The nucleus reuniens: a key node in the neurocircuitry of stress and depression. Mol Psychiatry. 2018;23(3):579-586. Liu J, Li L, Chen L, et al. Grey matter changes in Meige syndrome: a voxel-based morphology analysis. Sci Rep. 2020;10(1):14533. Burciu RG, Hess CW, Coombes SA, et al. Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms. Hum Brain Mapp. 2017;38(9):4563-4573. Glickman A, Nguyen P, Shelton E, Peterson DA, Berman BD. Basal ganglia and cerebellar circuits have distinct roles in blepharospasm. Parkinsonism Relat Disord. 2020;78:158-164. Jinnah HA, DeFazio G. Adult-onset focal dystonias: To lump or split. Int Rev Neurobiol. 2023;169:317-327. Brodoehl S, Wagner F, Prell T, Klingner C, Witte OW, Günther A. Cause or effect: Altered brain and network activity in cervical dystonia is partially normalized by botulinum toxin treatment. Neuroimage Clin. 2019;22:101792. Blood AJ, Kuster JK, Waugh JL, et al. White Matter Changes in Cervical Dystonia Relate to Clinical Effectiveness of Botulinum Toxin Treatment. Front Neurol. 2019;10:265. Nevrlý M, Hluštík P, Hok P, Otruba P, Tüdös Z, Kaňovský P. Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study. Exp Brain Res. 2018;236(10):2627-2637. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 May, 2024 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 05 Mar, 2024 Editor assigned by journal 05 Mar, 2024 Submission checks completed at journal 05 Mar, 2024 First submitted to journal 29 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4000528","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276435746,"identity":"9f08c9de-67cb-46f3-bac1-36a22abd42c6","order_by":0,"name":"Yuhan Luo","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Yuhan","middleName":"","lastName":"Luo","suffix":""},{"id":276435747,"identity":"40e5cf9e-3db4-4bd3-a573-3655bba8bb41","order_by":1,"name":"Huiming Liu","email":"","orcid":"","institution":"Sun Yat-Sen University Cancer 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Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYBACPmYg8aHChoGBmbkBJmiAVwsbUAvjjDNpQC2MxGoBYmbelsNAimgt7DzGL3gbzkfztzM2MP5sq0tsYG/eJsFQcwePw3jMLCR33M6dcZixgZm37XBiA8+xMgmGY8/wajEwPHM7twGkhbHtQGKDRI6ZBGPDYfxaEtvO5c4/DHOY/BuCWowfHGw7kLsBqIWBt40ZaAsPIS1sZYwNZ5JzNwK1HOY5d9i4jSet2CLhGG4t/PyHN3/+U2GXO+/84YMPf5TVyfazH95440MNbi0giyRgrAOMbJCYYkjApwEYkx8Q7D/4lY6CUTAKRsHIBADnFlNRnWDo4AAAAABJRU5ErkJggg==","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":true,"prefix":"","firstName":"Gang","middleName":"","lastName":"Liu","suffix":""},{"id":276435763,"identity":"1fdc6ead-9ad0-4730-a922-077f11637159","order_by":17,"name":"Jinping Xu","email":"","orcid":"","institution":"Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Jinping","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2024-02-29 16:31:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4000528/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4000528/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-024-03680-6","type":"published","date":"2024-05-24T00:27:22+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52195713,"identity":"11cde095-aff4-4334-9959-9864938ab065","added_by":"auto","created_at":"2024-03-07 19:54:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2263495,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe thalamic nucleus of one healthy participant. \u003c/strong\u003eThe images were shown using Freeview (https://surfer.nmr.mgh.harvard.edu/fswiki/FreeviewGuide).\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4000528/v1/f04dee12ca21fd0174d407de.png"},{"id":52195712,"identity":"9278f1dd-3ac3-4e8f-a709-cd2e7a52a338","added_by":"auto","created_at":"2024-03-07 19:54:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":666102,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDifferences of the thalamic nuclei volumes. \u003c/strong\u003eThalamic nuclei’s mean gray matter volumes were compared between idiopathic cervical dystonia and healthy controls using a general linear model with age, gender, and estimated total intracranial volume as covariates. The results were corrected by false discovery rate (FDR) with \u003cem\u003eP\u003c/em\u003e \u0026lt;0.05. * represents significant results. Abbreviations: iCD, idiopathic cervical dystonia, and HCs, healthy controls. The abbreviations of thalamic nuclei are listed in \u003cstrong\u003eTable 2\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4000528/v1/d3c855c85b03ebf58df579f4.png"},{"id":57115266,"identity":"ffc601a9-ccba-418f-a257-da3012ad9360","added_by":"auto","created_at":"2024-05-25 00:27:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5030267,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4000528/v1/c27718ec-b8ed-4574-af01-3c221b8714dd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Regional structural abnormalities in thalamus in idiopathic cervical dystonia","fulltext":[{"header":"Background","content":"\u003cp\u003eIdiopathic cervical dystonia (iCD), the most common form of adult-onset dystonia, is characterized by sustained or intermittent neck movements caused by involuntary muscle contractions, resulting in abnormal movements and postures of the head, neck, and/or shoulders. In addition, patients with iCD may also have nonmotor symptoms such as mood disorders, pain, cognitive deficits, and sleep disorders, together with motor manifestations that influence daily living activities and reduce the quality of life for the patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, the underlying cause and pathophysiology of iCD remain incompletely understood.\u003c/p\u003e \u003cp\u003eCurrent neurophysiological and neuroimaging evidence shows a network model in which various brain regions play a role in the iCD pathogenesis, including the basal ganglia, thalamus, cerebellum, and sensorimotor cortex [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The thalamus is a key integrative hub in this network, receiving and distributing information among different brain regions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Besides being a simple transponder, the thalamus contributes to signal processing within cortical hierarchies, involving in regulating emotions, arousal, cognition, wakefulness, motor control, and sensory information processing [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Lesion studies have shown that thalamic lesions are prone to induce CD [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], further emphasizing the potential key role of the thalamus in the iCD. Previous functional neuroimaging studies have shown increased cortical activation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], increased regional spontaneous brain activity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], glucose hyper-metabolism [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and altered functional connectivity profiles [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] in the thalamus and abnormal cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] in patients with iCD. Structural neuroimaging studies also revealed brain structural abnormalities in patients with iCD, but often yield diverse results. Either an increase [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] or a decrease [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]in thalamic volume has been reported in patients with iCD compared to healthy controls (HCs). Additionally, two neuroimaging studies investigating white matter microstructural abnormalities have identified increased fractional anisotropy in the bilateral thalamus in patients with iCD [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In these studies, the thalamus was considered a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. The thalamus contains distinct nuclei serving different functions, which may be related to different symptoms or disorders [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, to our knowledge, no studies have been conducted to explore structural alterations in the distinct thalamic nuclei and their relationship to the motor and nonmotor manifestations in patients with iCD. Recently, a statistical atlas of the thalamus was constructed using ultra-high-resolution ex vivo magnetic resonance imaging (MRI) combined with in vivo data [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] (available in FreeSurfer 7, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://surfer.nmr.mgh.harvard.edu/fswiki/rel7downloads\u003c/span\u003e\u003cspan address=\"https://surfer.nmr.mgh.harvard.edu/fswiki/rel7downloads\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). This tool enables the accurate measurement of each individual thalamic nuclei volume, exhibiting robust agreement with histological findings and showing excellent test-retest reliability [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The tool has recently been successfully employed to examine region-specific thalamic alterations in neurological disorders, including Parkinson\u0026rsquo;s disease [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], restless legs syndrome [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and epilepsy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], etc. Therefore, it is an ideal atlas to investigate whether and how thalamic nuclear volume change occurs in iCD.\u003c/p\u003e \u003cp\u003eIn this study, we analyzed structural MRI data from 37 patients with iCD and 37 HCs to examine: (1) whether gray matter-related abnormalities are only restricted to specific thalamic subregions; (2) whether and how alterations in volumes of thalamic subregions are associated with motor or nonmotor symptoms of patients with iCD. We hypothesized that there is heterogeneity in the morphological changes occurring within distinct thalamic nuclei in patients with iCD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003ePatients were recruited from our outpatient clinic for movement disorders between April 2019 and July 2023. The diagnosis of iCD was made by two senior neurologists based on the standard criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Patients were excluded if they: (i) had dystonia involving other body sites in addition to neck muscles; (ii) reported evidence of stroke, Parkinson\u0026rsquo;s disease, Alzheimer\u0026rsquo;s disease, epilepsy, and traumatic brain injury; (iii) had a family history of movement disorders as well as a history of exposure to antipsychotic drugs before the onset of dystonia; (iv) had any conditions that contradicted with cerebral MRI; (v) received botulinum toxin (BoNT) injections within 3 months and oral medications for approximately 24 h before MRI scans. HCs were also recruited using the same exclusion criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eClinical measurements\u003c/h2\u003e \u003cp\u003eThe demographics and clinical characteristics, including subjects\u0026rsquo; age, gender, education level, handedness, duration of disease, duration of BoNT injections, and times of BoNT injections, were collected via in-person interviews before MRI scanning. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], consisting of three subscales assessing motor severity, disability, and pain, was employed to evaluate symptom severity in patients with iCD by a trained neurologist. Furthermore, the Hamilton anxiety rating scale (HAMA) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], Hamilton depression rating scale (HAMD) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and Mini-Mental State Examination (MMSE) were also conducted before MRI scanning to evaluate patients\u0026rsquo; mood and cognitive function.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eImage acquisition\u003c/h2\u003e \u003cp\u003eThree-dimensional T1-weighted data were collected using a 3T MRI scanner (Tim Trio; Siemens, Erlangen, Germany) with a magnetization-prepared rapid-acquisition gradient-echo pulse sequence. The main parameters were repetition time\u0026thinsp;=\u0026thinsp;2530 ms; echo time\u0026thinsp;=\u0026thinsp;4.45 ms; inversion time\u0026thinsp;=\u0026thinsp;1100 ms; flip angle\u0026thinsp;=\u0026thinsp;7\u003csup\u003e○\u003c/sup\u003e; matrix dimensions\u0026thinsp;=\u0026thinsp;256 mm \u0026times; 256 mm; voxel size\u0026thinsp;=\u0026thinsp;1 \u0026times; 1 \u0026times; 1 mm\u003csup\u003e3\u003c/sup\u003e; and 192 slices.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eImage preprocessing\u003c/h2\u003e \u003cp\u003eAll T1 images were processed using the standard segmentation pipeline in FreeSurfer v7.1.1 with default settings (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://surfer.nmr.mgh.harvard.edu\u003c/span\u003e\u003cspan address=\"https://surfer.nmr.mgh.harvard.edu\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The main steps included skull stripping, Talairach registration and initialization of cortical surface reconstruction, cortical atlas registration, and subcortical parcellation. We implemented automatic parcellation of 25 thalamic nuclei in each hemisphere based on manual delineation combining in vivo and ex vivo data to quantify thalamic nuclei volumes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. These nuclei included anteroventral, laterodorsal and lateral posterior, ventral anterior, ventral anterior magnocellular, ventral lateral anterior, ventral lateral posterior (VLp), ventral posterolateral (VPL), and ventromedial (VM), central medial (CeM), central lateral, paracentral (Pc), centromedian (CM), and parafascicular (Pf), paratenial (Pt), Reuniens (medial ventral) (MV(Re)), mediodorsal medial magnocellular, and mediodorsal lateral parvocellular, lateral geniculate (LGN), medial geniculate (MGN), suprageniculate, pulvinar anterior, pulvinar medial, pulvinar lateral, and pulvinar inferior (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Visualized inspection confirmed that the automatic segmentation and labeling were performed accurately. Finally, Freeview (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://surfer.nmr.mgh.harvard.edu/fswiki/FreeviewGuide/FreeviewIntroduction\u003c/span\u003e\u003cspan address=\"https://surfer.nmr.mgh.harvard.edu/fswiki/FreeviewGuide/FreeviewIntroduction\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was used to show the thalamic nuclei.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eCalculation of thalamic nuclei volumes\u003c/h2\u003e \u003cp\u003eBetween-group differences of gray matter volume in the thalamic nuclei were performed using a general linear model with age, gender, and estimated total intracranial volume as covariates. Finally, the results were corrected by a false discovery rate (FDR) with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation analyses\u003c/h2\u003e \u003cp\u003eCorrelations between abnormal thalamic nuclei volumes and TWSTRS severity scores, disability scores, pain scores, disease durations, as well as HAMA and HAMD scores in patients with iCD were performed using partial correlations with age, gender, and estimated total intracranial volume as covariates. Meanwhile, correlations between HAMA/HAMD scores and TWSTRS severity scores, disability scores, pain scores, and disease durations in patients with iCD were also analyzed using partial correlations with age and gender as covariates. Statistical significance was set as \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eAge, estimated total intracranial volume, HAMA scores, HAMD scores, and MMSE scores were compared using two sample \u003cem\u003et\u003c/em\u003e-tests or Mann-Whitney \u003cem\u003eU\u003c/em\u003e tests after normality testing using the Shapiro-Wilk test. Pearson \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e test was performed for gender comparison. All analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 25.0 (SPSS Inc., Chicago, IL).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eDemographic information and clinical characteristics\u003c/h2\u003e \u003cp\u003eFinally, 37 patients with iCD and 37 HCs were included in this study. However, the TWSTRS, HAMD, and MMSE scores were completed by 29, 36, and 35 patients with iCD, respectively. The primary reason for incomplete clinical evaluations in certain patients is their discomfort experienced from abnormal movements and postures, leading to their refusal to cooperate with long-term scale assessment. The clinical and demographic information of the 37 patients with iCD and 37 HCs are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The iCD and HCs groups did not differ in gender, estimated total intracranial volume, and MMSE scores. There were significant differences in age, HAMA, and HAMD scores between patients with iCD and HCs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParticipants\u0026rsquo; demographics and clinical characteristics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eiCD (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHCs (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGender (Female/Male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17/20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24/13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian age, years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (19\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (33\u0026ndash;55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eeTIV, cm\u003csup\u003e3\u003c/sup\u003e (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1459 (935\u0026ndash;1787)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332 (924\u0026ndash;1883)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian MMSE scores (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (25\u0026ndash;30)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (25\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.221\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian HAMA scores (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian HAMD scores (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (0\u0026ndash;18)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0\u0026ndash;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDisease duration, years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 (0.12-13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBoNT injections (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian TWSTRS severity scores (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (7\u0026ndash;25)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian TWSTRS disability scores (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (0\u0026ndash;23)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMedian TWSTRS pain scores (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5 (0\u0026ndash;14)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: \u003csup\u003ea\u003c/sup\u003e only 35 subjects were available. \u003csup\u003eb\u003c/sup\u003e only 36 subjects were available. \u003csup\u003ec\u003c/sup\u003e only 29 subjects were available. Abbreviations: BoNT, Botulinum toxin; eTIV, estimated total intracranial volume; iCD, idiopathic cervical dystonia; HAMA, Hamilton anxiety rating scale; HAMD, Hamilton depression rating scale; HCs, healthy controls; MMSE, Mini-Mental State Examination; and TWSTRS, Toronto Western Spasmodic Torticollis Rating Scale.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDifferences of the thalamic nuclei volumes\u003c/h2\u003e \u003cp\u003ePatients with iCD compared to HCs showed significant volume atrophy mainly in the CeM, CM, LGN, MGN, MV(Re), Pc, Pf, Pt, and VM nuclei (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, FDR corrected; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Trends for volume reduction of VLp (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.053, FDR corrected) and VPL (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.057, FDR corrected) nuclei were also observed in patients with iCD relative to HCs (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifferences of thalamic nuclei volumes between idiopathic cervical dystonia and healthy controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThalamic Nucleus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbbreviations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHCs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eiCD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCorrected \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnteroventral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e271.17\u0026thinsp;\u0026plusmn;\u0026thinsp;39.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e269.45\u0026thinsp;\u0026plusmn;\u0026thinsp;34.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral medial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCeM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139.95\u0026thinsp;\u0026plusmn;\u0026thinsp;20.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e134.94\u0026thinsp;\u0026plusmn;\u0026thinsp;18.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.032*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral lateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.09\u0026thinsp;\u0026plusmn;\u0026thinsp;18.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.66\u0026thinsp;\u0026plusmn;\u0026thinsp;12.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentromedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e513.31\u0026thinsp;\u0026plusmn;\u0026thinsp;68.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e499.73\u0026thinsp;\u0026plusmn;\u0026thinsp;68.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.044*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLateraldorsal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.03\u0026thinsp;\u0026plusmn;\u0026thinsp;15.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.80\u0026thinsp;\u0026plusmn;\u0026thinsp;12.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLateral geniculate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLGN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e589.09\u0026thinsp;\u0026plusmn;\u0026thinsp;76.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e571.24\u0026thinsp;\u0026plusmn;\u0026thinsp;79.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.032*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLateral posterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e240.39\u0026thinsp;\u0026plusmn;\u0026thinsp;46.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e245.27\u0026thinsp;\u0026plusmn;\u0026thinsp;29.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimitans (suprageniculate)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL-Sg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.47\u0026thinsp;\u0026plusmn;\u0026thinsp;7.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.44\u0026thinsp;\u0026plusmn;\u0026thinsp;10.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMediodorsal lateral parvocellular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e522.70\u0026thinsp;\u0026plusmn;\u0026thinsp;46.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e518.38\u0026thinsp;\u0026plusmn;\u0026thinsp;51.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMediodorsal medial magnocelluar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1500.73\u0026thinsp;\u0026plusmn;\u0026thinsp;161.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1491.45\u0026thinsp;\u0026plusmn;\u0026thinsp;163.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedial geniculate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMGN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e234.22\u0026thinsp;\u0026plusmn;\u0026thinsp;27.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e221.81\u0026thinsp;\u0026plusmn;\u0026thinsp;32.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.045*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReuniens (medial ventral)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMV(Re)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.54\u0026thinsp;\u0026plusmn;\u0026thinsp;4.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.032*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParacentral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.046*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParafascicular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePf\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122.30\u0026thinsp;\u0026plusmn;\u0026thinsp;19.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e116.67\u0026thinsp;\u0026plusmn;\u0026thinsp;16.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.032*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParatenial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.044*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulvinar anterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePuA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e439.48\u0026thinsp;\u0026plusmn;\u0026thinsp;38.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e452.30\u0026thinsp;\u0026plusmn;\u0026thinsp;46.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.385\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulvinar inferior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePuI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e521.98\u0026thinsp;\u0026plusmn;\u0026thinsp;73.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e552.26\u0026thinsp;\u0026plusmn;\u0026thinsp;83.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulvinar lateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePuL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e377.68\u0026thinsp;\u0026plusmn;\u0026thinsp;46.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e398.42\u0026thinsp;\u0026plusmn;\u0026thinsp;59.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulvinar medial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePuM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2268.23\u0026thinsp;\u0026plusmn;\u0026thinsp;254.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2359.87\u0026thinsp;\u0026plusmn;\u0026thinsp;260.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.458\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentral anterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e805.43\u0026thinsp;\u0026plusmn;\u0026thinsp;89.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e817.68\u0026thinsp;\u0026plusmn;\u0026thinsp;88.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentral anterior magnocellular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVAmc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.33\u0026thinsp;\u0026plusmn;\u0026thinsp;8.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.18\u0026thinsp;\u0026plusmn;\u0026thinsp;7.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentral lateral anterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVLa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1258.57\u0026thinsp;\u0026plusmn;\u0026thinsp;146.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1261.48\u0026thinsp;\u0026plusmn;\u0026thinsp;138.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentral lateral posterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVLp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1659.83\u0026thinsp;\u0026plusmn;\u0026thinsp;206.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1652.35\u0026thinsp;\u0026plusmn;\u0026thinsp;195.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentromedial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.70\u0026thinsp;\u0026plusmn;\u0026thinsp;8.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.63\u0026thinsp;\u0026plusmn;\u0026thinsp;9.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.044*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentral posterolateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVPL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1918.61\u0026thinsp;\u0026plusmn;\u0026thinsp;250.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1879.88\u0026thinsp;\u0026plusmn;\u0026thinsp;261.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: * represents significant results after false discovery rate (FDR) corrected with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Abbreviations: iCD, idiopathic cervical dystonia, and HCs, healthy controls.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eCorrelational analyses\u003c/h2\u003e \u003cp\u003eNo statistically significant correlations were observed between altered thalamic nuclei volumes and TWSTRS severity scores, disability scores, pain scores, disease durations, HAMA scores, and HAMD scores in patients with iCD after adjusting for age, gender and estimated total intracranial volume as covariates. Moreover, no statistically significant correlations were observed between HAMA/HAMD scores, TWSTRS scores, and disease durations in patients with iCD with age and gender as covariates.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we observed a significant decrease in gray matter volume of specific thalamic nuclei, including CeM, CM, LGN, MGN, MV(Re), Pc, Pf, Pt, and VM in patients with iCD compared to HCs. However, no statistically significant correlations were found between these thalamic nuclei volumes and clinical characteristics in iCD group. These results support the hypothesis that regional thalamic atrophy is present in patients with iCD.\u003c/p\u003e \u003cp\u003eThe intralaminar thalamic nuclei are the primary source of excitatory input from the thalamus to the striatum [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The caudal group of intralaminar thalamic nuclei, namely the CM and Pf nuclei, exhibit extensive and specific connections with the basal ganglia and motor cortex, indicating potential involvement of the CM-Pf complex in motor functions. Projections from the CM and Pf are principally to the striatum, which have been shown to mediate a reciprocal thalamostriatal interaction that plays an important role in both normal and pathological movement [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Semenova and his colleagues discovered that movement-sensitive CM-Pf neurons exhibit selective sensitivity towards voluntary neck and hand movements in patients with iCD [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The most pronounced and prolonged responses were observed during movements involving neck muscles and involuntary dystonic movements, indicating the participation of the CM-Pf complex in motor behavior and its potential involvement in the pathophysiology of iCD. However, because of the absence of a control group in this study, whether these findings are directly relevant to the disease\u0026rsquo;s pathophysiology remains uncertain [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Our findings that CM and Pf nuclei atrophy was found in patients with iCD, may further provide evidence for their involvement in the pathophysiology of iCD. Projections from intralaminar nuclei transmit sensory signals to striatal cholinergic interneurons, eliciting a lasting pause after a burst of spikes and facilitating the integration of cortical inputs with medium spiny neurons, thereby playing a crucial role in motor function [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. A study on mice carrying the DYT1 dystonia mutation demonstrated that an altered thalamostriatal input pattern leads to abnormal cholinergic signaling, disrupting the integration between corticostriatal and thalamostriatal, which might result in an altered motor output and predispose DYT1 gene mutation carriers to develop dystonic movements [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Furthermore, the thalamic rostral intralaminar nuclei, including the CeM and Pc nuclei, contribute to a range of behaviors such as sensorimotor coordination, pain modulation, cognition, and arousal processing through extensive projections to the striatum and cortex [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Among these nuclei, Pc contributes to motor control and processes pain signals conveyed through the spinoparabrachial pathway [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Sensory symptom, such as pain, is commonly reported in patients with iCD [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]; however, the underlying pathophysiological mechanism of this nonmotor manifestation remains unclear. It is reasonable to speculate that such symptom might be caused by the dysfunction of Pc nucleus in iCD. In functional MRI studies, iCD has been considered a consequence of an abnormal basal ganglia-thalamo-cortical circuit [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, the present findings might improve our understanding of the role of underlying structural substrates in abnormal functional brain states in iCD.\u003c/p\u003e \u003cp\u003eThe exploration of ventral thalamic nuclei is particularly interesting because of their involvement in sensorimotor information processing and being one of the major targets for surgical treatment of movement disorders [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. It has been reported that four patients with iCD received markedly improved dystonic head tremor and dystonia after continuous bilateral thalamic ventral lateral anterior nucleus stimulation for 3 months [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Previous studies have identified specific patterns of neuronal activity and pathological features of the ventral thalamus in iCD [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Ventral thalamic neurons exhibiting dystonia-frequency activity in patients with iCD and suppression of this activity induced immediate improvement and subsequent further enhancement of dystonic movement and posture, revealing the critical role of the ventral thalamus as a key node within the network associated with dystonia [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. In our study, we observed that patients with iCD exhibited atrophy in the thalamus\u0026rsquo;s VM, VLp, and VPL nuclei. However, the latter two nuclei differences between groups did not reach statistical significance via FDR correction. VM and VLp are known as the motor thalamus, connecting the motor areas of the cerebral cortex to the basal ganglia and cerebellum [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. VPL, as a part of the somatosensory thalamus, receives neuronal input from the medial lemniscus and spinothalamic tracts and subsequently projects to the somatosensory cortex [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Furthermore, proprioceptive signals from neck muscles have historically been considered to project to the VPL nucleus [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Abnormalities in the integration of sensory input with control of motor output in focal dystonia have been highlighted by recent neurophysiological studies [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Therefore, the impaired sensory-motor integration may be partly explained by atrophy in these subregions of the thalamus in patients with iCD.\u003c/p\u003e \u003cp\u003eOur study also revealed a higher prevalence of anxiety (37.8%) and depressive symptoms (36.1%) in patients with iCD compared to HCs. Furthermore, no significant correlations were found between HAMA/HAMD scores and the severity of motor symptoms or disease duration in patients with iCD, demonstrating that mood disorders are not simply a consequence of the movement disorder. Consistent with our results, higher rates of all psychiatric comorbidities were observed in those with iCD, with depression and anxiety being the most commonly diagnosed. Additionally, anxiety and depressive symptoms were reported to precede the onset of iCD generally and reach a peak 12 months before dystonia diagnosis, indicating that both psychiatric disorders are either prodromal symptoms or reflect shared aetiological mechanisms [\u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. However, research on the mechanisms underlying anxiety or depressive symptoms in iCD is relatively limited. Current studies propose dysfunction within basal ganglia-thalamo-cortical circuits underlies motor and psychiatric manifestations in iCD [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. In line with this hypothesis, growing evidence shows that the thalamus is one of the core dysconnectivity nodes in anxiety and depression [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The Re nucleus, a thalamic midline nucleus, exhibits reciprocal connections with the prefrontal cortex and hippocampus, serving as key intermediaries between these structures to regulate emotional behaviors [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Previous animal studies have indicated the involvement of Re nucleus dysfunction in anxiety and depressive-like behavior, which may contribute to the amalgamation of symptoms commonly observed in mental disorders such as anxiety and depression [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. Interestingly, our study also identified atrophy in the Re nucleus in patients with iCD. Therefore, we speculate that volumetric changes in this specific thalamic region may associated with mood disorders observed in iCD. A voxel-based morphometry study investigating another type of cranial dystonia with and without depression partially supported our hypothesis by revealing volume reduction in the frontal cortex and hippocampus in the depression group. However, it is with regret that this study did not specifically examine morphometric differences within thalamic nuclei [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Further research is needed to understand the underlying pathophysiology of anxiety and depression in patients with iCD.\u003c/p\u003e \u003cp\u003eUnfortunately, we did not find any correlations between atrophy in these thalamic nuclei and the severity of motor symptoms in patients with iCD, which appears to contradict the current view that implicates the involvement of the cerebello-thalamo-cortical circuit in symptom severity across different types of focal dystonia [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. A plausible explanation could be that while a potential mechanism involves a similar network model responsible for focal dystonia, different types of dystonia originate from dysfunction in one of these regions before impacting the network more extensively. In other words, diverse forms of focal dystonia might emerge at different levels within the network, resulting in nodes with varying hierarchies of influence and specific roles. Only structural abnormalities in high-order nodes might determine the severity of symptoms in patients with iCD [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. In line with our results, previous neuroimaging studies on patients with iCD also reported a lack of correlations between reduced thalamic volume and symptom severity [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Moreover, another study demonstrated that only thalamic connections to other brain regions were altered when symptoms improved after BoNT treatment in iCD, without affecting its loss of responsiveness [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Additionally, patients with unavailable TWSTRS scores might potentially influence the correlations between those and changes in thalamic nuclei volume. Further investigation is needed to understand the role of specific thalamic nuclei within the network model of iCD.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, our sample size is relatively small, which may limit the statistical power to detect significant differences in VLp and VPL nuclei volumes between groups after FDR corrections and correlations between atrophy in thalamic nuclei and severity in motor and nonmotor symptoms in patients with iCD. Second, the iCD and HCs groups are not matched for age, though we have regressed age and intracranial volume as covariates when comparing differences of the thalamic nuclear volumes between the two groups to mitigate its effect. Third, some patients\u0026rsquo; lack of TWSTRS scores might influence the correlations between those and altered thalamic nuclei volume. Finally, some previous studies have demonstrated that BoNT injections can induce alterations in subcortical white matter microstructure [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e] and sensorimotor network activation [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e] in patients with iCD. The effects of BoNT on the thalamic nuclei volumes were not assessed in this study. Further studies should be considered to address this limitation.\u003c/p\u003e \u003cp\u003eIn conclusion, our findings demonstrate that patients with iCD exhibit atrophy in specific thalamic nuclei, particularly the intralaminar and ventral thalamic nuclei, highlighting the crucial role of the thalamus in the pathophysiology of iCD. The thalamus should not be considered a single, homogeneous structure because of potentially useful information about distinct thalamic nuclei in future dystonia studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBoNT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; botulinum toxin\u003c/p\u003e\n\u003cp\u003eCeM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; central medial\u003c/p\u003e\n\u003cp\u003eCM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; centromedian\u003c/p\u003e\n\u003cp\u003eFDR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; false discovery rate\u003c/p\u003e\n\u003cp\u003eHAMA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hamilton anxiety rating scale\u003c/p\u003e\n\u003cp\u003eHAMD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Hamilton depression rating scale\u003c/p\u003e\n\u003cp\u003eHCs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;healthy controls\u003c/p\u003e\n\u003cp\u003eiCD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; idiopathic cervical dystonia\u003c/p\u003e\n\u003cp\u003eLGN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; lateral geniculate\u003c/p\u003e\n\u003cp\u003eMGN \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;medial geniculate\u003c/p\u003e\n\u003cp\u003eMMSE \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mini-Mental State Examination\u003c/p\u003e\n\u003cp\u003eMRI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eMV(Re) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Reuniens (medial ventral)\u003c/p\u003e\n\u003cp\u003ePc \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; paracentral\u003c/p\u003e\n\u003cp\u003ePf \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; parafascicular\u003c/p\u003e\n\u003cp\u003ePt \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; paratenial\u003c/p\u003e\n\u003cp\u003eSPSS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Statistical Package for the Social Sciences\u003c/p\u003e\n\u003cp\u003eTWSTRS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Toronto Western Spasmodic Torticollis Rating Scale\u003c/p\u003e\n\u003cp\u003eVLp \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; ventral lateral posterior\u003c/p\u003e\n\u003cp\u003eVM \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;ventromedial\u003c/p\u003e\n\u003cp\u003eVPL \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; ventral posterolateral\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe declare that all experiments on human subjects were conducted in accordance with the Declaration of Helsinki and that all procedures were carried out with the adequate understanding and written consent of the subjects. We also certify that formal approval to conduct the experiments described has been obtained from the human subjects review board of our institution (the Ethical Committee of the First Affiliated Hospital of Sun Yat-Sen University) and could be provided upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData and materials availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and materials supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the National Natural Science Foundation of China (grant numbers 62006220, 81771137, 82271300, and 81971103), Natural Science Foundation of Guangdong Province (grant numbers 2023A1515012739, 2016A030310132, and 2021A1515010600), Guangdong Key Project (grant numbers 2018B030335001 and 2023A1515012739), Guangzhou Key Project (grant number 202007030002), Science and Technology Program of Guangzhou (grant number 2023B03J0466), Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases (grant number 2020B1212060017), Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (grant numbers 2015B050501003 and 2020A0505020004), Shenzhen Science and Technology Research Program (grant number JCYJ20200109114816594), Guangdong Provincial Engineering Center for Major Neurological Disease Treatment, and Guangdong Provincial Translational Medicine Innovation Platform for Diagnosis and Treatment of Major Neurological Disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGL and JPX:\u0026nbsp;Conceptualization; JPX and QMH: Methodology; YHL, HML, LCZ, AW, ZKY, YZ, JNZ, ZLO, ZCY, QXC, XXF, XDZ, WXZ, GL and JPX: Formal analysis and investigation; QXC, XXF, XDZ, QMH, KQP, and YWW: validation; YHL, HML, GL and JPX: writing-original draft; ZLO, ZCY, QMH, WXZ, YWW, GL and JPX: writing-review \u0026amp; editing; GL: Supervision; GL: data curation. All authors have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.cn) for English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlbanese A, Bhatia KP, Cardoso F, et al. Isolated Cervical Dystonia: Diagnosis and Classification. Mov Disord. 2023;38(8):1367-1378. \u003c/li\u003e\n\u003cli\u003eJinnah HA, Neychev V, Hess EJ. The Anatomical Basis for Dystonia: the Motor Network Model. Tremor Other Hyperkinet Mov (NY). 2017;7:506. \u003c/li\u003e\n\u003cli\u003eHuang X, Zhang M, Li B, Shang H, Yang J. Structural and functional brain abnormalities in idiopathic cervical dystonia: a multimodal meta-analysis. Parkinsonism Relat Disord. 2022;103:153-165.\u003c/li\u003e\n\u003cli\u003eHwang K, Bertolero MA, Liu WB, D\u0026apos;Esposito M. 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Exp Brain Res. 2018;236(10):2627-2637.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"atrophy, gray matter volume, idiopathic cervical dystonia, structural magnetic resonance imaging, thalamic nuclei","lastPublishedDoi":"10.21203/rs.3.rs-4000528/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4000528/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAlthough the thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD), the nature of the alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eStructural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analyzed in patients with iCD.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCompared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study highlights the neurobiological mechanisms of iCD related to thalamic changes.\u003c/p\u003e","manuscriptTitle":"Regional structural abnormalities in thalamus in idiopathic cervical dystonia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-07 19:53:59","doi":"10.21203/rs.3.rs-4000528/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-03-05T07:40:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-05T07:24:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-05T06:46:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-02-29T16:00:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"af0186c4-57f1-408a-bad9-944c32c98309","owner":[],"postedDate":"March 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-25T00:27:22+00:00","versionOfRecord":{"articleIdentity":"rs-4000528","link":"https://doi.org/10.1186/s12883-024-03680-6","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2024-05-24 00:27:22","publishedOnDateReadable":"May 24th, 2024"},"versionCreatedAt":"2024-03-07 19:53:59","video":"","vorDoi":"10.1186/s12883-024-03680-6","vorDoiUrl":"https://doi.org/10.1186/s12883-024-03680-6","workflowStages":[]},"version":"v1","identity":"rs-4000528","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4000528","identity":"rs-4000528","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}